The conduct and reporting of mediation analysis in recently published randomized controlled trials : results from a methodological systematic review

Objectives: To describe the methodological characteristics of mediation analyses (MAs) reported in recent randomized controlled trials (RCTs) and to propose recommendations on the planning, conduct, and reporting of MAs in practice. Study Design and Setting: We conducted a systematic review by searching MEDLINE (January 1, 2017, to December 1, 2018) for all reports of RCTs or secondary analyses of previously published RCTs that reported a MA. Two reviewers independently screened the title, abstracts, and full texts of the identified reports and extracted the data from the 98 eligible studies. Results: MAs were nearly always (96%) based on a traditional mediation approach. Most studies did not report a sample size calculation for the MA (96%) or assess potential treatment-by-mediator interactions (96%). In 53% of studies, mediators and outcomes were simultaneously measured. In 57% of studies, mediator-mediator and mediator-outcome confounders were adjusted for in the analysis, although adjustment was often limited to few potential confounders. About 30% of studies discussed the assumptions underlying the MA. Conclusion: The conduct and reporting of MAs remained quite heterogeneous in practice. Future MAs could benefit from a consensus-based planning, conduct, and reporting guideline for MA

Measuring review report quality in health research : development and validation of ARCADIA

Tesi en modalitat de cotutela: Universtat Politècnica de Catalunya i Université de Paris. Aplicat embargament des de la data de defensa fins el 31 de desembre de 2021Editorial peer review is the gateway to scientific publication. It was established to ensure that research papers were vetted by independent experts before they are published. Despite the importance of this process, its impact is still considered suboptimal and it needs to be improved. For this purpose, we need appropriate outcome measures, particularly a validated tool that clearly defines the quality of peer review reports. The final aim of the present PhD project was to develop and validate a new tool for assessing the quality of peer review reports in biomedical research. As the starting point for the development of a new tool, we performed a systematic review aimed to identify and describe the existing tools used to assess peer review report quality in biomedical research. We identified a total number of 24 tools: 23 scales and 1 checklist. None of the tools reported a definition of ‘quality’. Only one described the scale development and 10 provided measures of validity and reliability. We classified the quality components of the 18 tools with more than one item into 9 main quality domains and 11 subdomains. Secondly, we formed a steering committee composed of five members with diverse expertise, which defined the quality of peer review reports. We then conducted an online survey intended for biomedical editors and authors to 1) determine if participants endorsed the proposed definition of peer review report quality; 2) identify the most important items to include in the tool, and 3) identify any missing items. Based on the participants’ qualitative and quantitative answers, the steering committee modified the initially proposed definition of peer review report quality, reviewed all items, and ultimately, drafted and refined the final version of the tool. The ARCADIA (Assessment of Review reports with a Checklist Available to eDItors and Authors) tool was finally developed. The tool is a checklist that includes 14 items encompassed in 5 domains. Each item should be ticked as ‘Yes’ or ‘No’. However, an item could also be assessed as ‘Not applicable’ (NA) depending on the reviewer’s expertise, type of study, type of biomedical journal, availability of study data, materials and protocol. Finally, we tested the tool and evaluated its acceptability, reliability, and validity. ARCADIA was validated by a heterogeneous sample of both biomedical editors and authors using a sample of peer review reports from two different biomedical journals (i.e., The BMJ and BMJ Open). Field-testing demonstrated that the psychometric properties of ARCADIA are not entirely satisfactory. Results from the validation study should be used to inform a new version of the ARCADIA tool, which should be also validated in a real-editorial setting using peer review reports associated with manuscripts with different study designs and from different types of journals. This thesis reports the development and validation of ARCADIA, a new tool for assessing the quality of peer review reports in biomedical research. ARCADIA constitutes the first tool that has been systematically developed to assess the quality of peer review reports and its validation is based on a large and diverse sample of biomedical editors and authors. This tool could be used regularly by editors to evaluate the reviewers' work, and also as an outcome when evaluating interventions to improve the peer review process.La revisión editorial por pares es la puerta de entrada a la publicación científica. Se estableció para garantizar que los artículos de investigación fueran examinados por expertos independientes antes de su publicación. A pesar de la importancia de este proceso, su impacto aún se considera subóptimo y debe mejorarse. Para este propósito, necesitamos outcomes apropiados, particularmente una herramienta validada que defina claramente la calidad de los informes de revisión por pares. El objetivo final del presente proyecto de doctorado fue desarrollar y validar una nueva herramienta para evaluar la calidad de los informes de revisión por pares en la investigación biomédica. Como punto de partida para el desarrollo de una nueva herramienta, realizamos una revisión sistemática destinada a identificar y describir las herramientas existentes que se utilizan para evaluar la calidad de los informes de revisión por pares en la investigación biomédica. Identificamos un total de 24 herramientas: 23 escalas y 1 lista de comprobación. Ninguna de las herramientas incorporó una definición de `calidad¿. Solo una describió el desarrollo de la escala y 10 proporcionaron medidas de validez y confiabilidad. Clasificamos los componentes de calidad de las 18 herramientas con más de un elemento en 9 dominios de calidad principales y 11 subdominios. En segundo lugar, formamos un comité directivo compuesto por cinco miembros con experiencia diversa que definieron la calidad de los informes de revisión por pares. Luego, realizamos una encuesta online destinada a editores y autores biomédicos para 1) determinar si los participantes respaldaban la definición propuesta de calidad del informe de revisión por pares; 2) identificar los ítems más importantes para incluir en la herramienta; y 3) identificar cualquier ítem faltante. Sobre la base de las respuestas cualitativas y cuantitativas de los participantes, el comité directivo modificó la definición propuesta inicialmente de calidad del informe de revisión por pares, revisó todos los ítems y, por último, redactó y perfeccionó la versión final de la herramienta. Seguidamente se desarrolló la herramienta ARCADIA (Assessment of Review reports with a Checklist Available to eDItors and Authors). La herramienta es una lista de comprobación que incluye 14 elementos englobados en 5 dominios. Cada elemento debe marcarse como "Sí" o "No". Sin embargo, un elemento también podría evaluarse como `No aplicable¿ (NA) según la experiencia del revisor, el tipo de estudio, el tipo de revista biomédica, la disponibilidad de los datos del estudio, los materiales y el protocolo. Finalmente, probamos la herramienta y evaluamos su aceptabilidad, fiabilidad y validez. ARCADIA fue validada por una muestra heterogénea de editores y autores biomédicos utilizando informes de revisión por pares de dos revistas biomédicas diferentes (es decir, The BMJ y BMJ Open). Las pruebas de campo demostraron que las propiedades psicométricas de ARCADIA no son del todo satisfactorias. Los resultados del estudio de validación deben usarse para impulsar una nueva versión de la herramienta ARCADIA, que también debe validarse en un entorno editorial real utilizando informes de revisión por pares asociados con manuscritos con diferentes diseños de estudio y de diferentes tipos de revistas. Esta tesis informa sobre el desarrollo y validación de ARCADIA, una nueva herramienta para evaluar la calidad de los informes de revisión por pares en la investigación biomédica. ARCADIA constituye la primera herramienta que se ha desarrollado sistemáticamente para evaluar la calidad de los informes de revisión por pares, validada con una amplia y diversa muestra de editores y autores biomédicos. Los editores podrían utilizar esta herramienta con regularidad para evaluar el trabajo de los revisores y también como variable respuesta al evaluar intervenciones para mejorar el proceso de revisión por pares.Postprint (published version

Asymmetric conjugate additions of dialkylzinc reagents to enones promoted by new purely atropisomeric phosphoramidite ligands

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Effect of dietary administration of oil extract from rosemary on reproductive efficiency in boars

A decrease in reproductive performance in boars during and immediately after hot summer weather has been previously reported (Park and Yi, 2002). High temperature causes germ-cell destruction and results in a temporary decrease in sperm production and fertility. The increase of metabolic activity following thermic stress matches with a higher production of free radicals that impairs cells, such as spermatozoa, particularly rich in polyunsatured fatty acids and poor in antioxidants systems

5,5,7,7-Tetrametyl-6,7-dihydro-5H-dibenzo[c,e]azepine

5,5,7,7-Tetrametyl-6,7-dihydro-5H-dibenzo[c,e]azepine has been synthesized as a possible pro-chiral (or tropos) unit for the construction of a chiral catalyst and as a molecular chirality sensor for the absolute configuration assignment by chiroptical spectroscopy. A straightforward synthetic strategy for the preparation of the title compound in high overall yield through sequential addition of the four methyl groups on benzylic positions has been described. A VT-NMR study was used to determine the rotational barrier of the aryl-aryl bond in this biphenylazepine, revealing its torsional flexibility at room temperature, which makes the biphenylazepine suitable as both a chirality probe and a tropos moiety in chiral ligands

Body weight estimation from body measures in Cornigliese sheep breed

The aim of this research is to propose equations to estimate body weight (BW) from body measures (BMs) in the Cornigliese sheep, an endangered breed reared in Italy for meat purpose. BW and BMs were submitted to correlation and multiple regression analyses. Two datasets were used: (i) 303 animals (178 females, 125 males, BW 4.00–117.80 kg), on which BW, height at withers (HW), chest circumference (ChC) and body length (BL) were measured; (ii) 156 animals (109 females, 47 males, BW 5.15–117.80 kg) out of 303 on which croup height (HCr), chest width (ChW), chest depth (ChD) and croup width (CrW) were also considered. On each dataset, two regression models were applied, one containing all variables (models 1 and 3, respectively, for datasets 1 and 2) and the other one comprising groups of variables, selected by means of the stepwise procedure (models 2 and 4, respectively, for datasets 1 and 2). BW resulted correlated with all BMs (from 0.852 for ChW to 0.950 for ChC; p < .001). Models 1 and 3 fitted the data better than models 2 and 4, both for all animals and for females and males separately. We concluded that BW could be predicted from BMs also in Cornigliese sheep breed. The best fits were obtained when the highest number of measures was included in the model (models 1 and 3). Nevertheless, models 2 and 4 could be used more easily in extensive sheep breeding than models 1 and 3, since they require less parameters.Highlights The estimation of body weight is important in a meat type sheep breed for choosing the optimal slaughter time. A reduction of work for farmer is positive, mainly in field conditions of extensive rearing, where scales are not easily available. Body weight could be predicted from body measures in Cornigliese sheep breed with good precision and accuracy

Effect of Duroc genes proportion on growth performance and on carcass and meat quality characteristics in heavy pigs

By means of the application of covariance models, the linear effects of the proportion of Duroc genes were evaluated with respect to growth (from 6 to 170 kg live weight) and feed/gain ratios, as well as carcass (lean cuts, adipose cuts, linear measures, backfat thickness, loin area and lean percentage) and meat quality (L* a* b* colour, reflectance, electrical conductivity, pH) in 167 heavy pigs (87 castrated males, 80 females) from different crosses of Duroc (D), Large White (LW) and Landrace (L) breeds, from 25 to approximately 300 d of age. The pigs were weighed at 25, 105, 170, 235 d and at the end of the trial (298 ± 6 d of age), and were raised under the same conditions. The proportion of Duroc genes was 0% (LWxL; no. 33), 25% [(LWx(DxL); n. 31 and Lx(DxLW); n. 35)] and 50% [Dx(LWx(LWxL)); n. 68]. The increase in the proportion of Duroc genes negatively affected the live weight at the different ages (P0.10). In fact, during the final phase (from 120 to 170 kg l.w.) the effect of the Duroc breed on daily gain became positive (P=0.08), and the feed/gain ratios were significantly lower (P=0.02). The carcass composition was not significantly influenced by the increase in the proportion of Duroc genes, with the exception of a rise in the weight of neck (P<0.01) and flare fat (P=0.02) and a reduction of ham (P=0.09). Carcass length resulted lower as the proportion of Duroc genes increased (P<0.01); at 24 h from slaughtering, meat colour showed lower values for lightness (P=0.08), redness (P=0.02) and yellowness (P=0.03)

Monitoring blood plasma leptin and lactogenic hormones in pregnant sows.

The mechanism of action of leptin in pregnant breeding sows, in which hyperphagia is managed through dietary strategies, is yet to be clarified. The aim of this study was to monitor leptin concentrations and their interactions with lactogenic hormones in Large White×Landrace breeding multiparous sows (n=15). All sows showed a normal body condition (mean body condition score: 2.96). Blood samples were collected the day after weaning the litters, at insemination, every 15 days up to day 45 of pregnancy and every 7 days from day 46 to farrowing. At delivery, the placenta was collected for the analysis of leptin and leptin receptor expressions. Plasma leptin levels increased from the end of mid gestation (day 72) and remained high until farrowing (P<0.05). As expected, plasma prolactin (PRL), low during most of pregnancy, increased during the 2 weeks before farrowing (P<0.05), whereas progesterone levels reached plateau at 30 days of gestation and decreased at farrowing (P<0.05). Cortisol levels peaked close to farrowing (P<0.05). Leptin was expressed in the placenta, where the receptor expression analysis showed the presence of the short form but not of the long form. A positive correlation was found between leptin and PRL concentrations during mid (r=0.430; P<0.001) and late (r=0.687; P<0.001) pregnancy, and with progesterone in early pregnancy (r=0.462; P<0.05). During late gestation, a positive correlation was observed between leptin and cortisol (r=0.585; P<0.001). Our results suggested that, in restrictively fed pregnant sows, the leptin levels increased from the end of mid pregnancy to delivery, confirming the presence of leptin resistance. We showed a correlation between leptin and lactogenic hormones during different stages of pregnancy in sows. Lactogenic hormones show pregnancy-specific changes in their secretion and all may become involved in modulating leptin signal

Effect of sex and season of birth on Gompertz growth curve parameters in "Nero di Parma" pigs

The growth curves of “Nero di Parma” pigs were studied by applying the Gompertz equation to 1069 body weight (BW) records from 285 pigs (156 females, 129 castrated males) born in 11 outdoor and 5 indoor herds; pigs were fed commercial complete feeds offered ad libitum and, on a limited basis in the outdoor system, diets were integrated with pasture. The parameters of the Gompertz equation were compared with reference to sex and season of birth. Mature BW for castrated males (229.0 kg) was 3.5% greater than that for females (221.3 kg) (P180 kg)

Carcass and meat parameters in Cornigliese sheep breed as affected by sex and age-class

A total of 72 animals from Cornigliese sheep breed were reared under homogeneous conditions, with the aim to assess the effect of sex (males, females) and age-class (heavy lambs, adults) on carcass and meat parameters. A model with fixed effects of herd, sex, slaughtering session, age-class and interaction (sex*age-class) was used; for slaughter data, the carcass weight was used as a covariate. The age-class effect was significant for most of the carcass measurements, indicating a late development in animals. Also, slaughter performance was significantly affected by age-class, with higher values (p<0.05) of hot carcass yield shown by heavy lambs than by adults. Carcass compactness index was lower in heavy lambs than in adults (p<0.001), and the lowest value (0.283; p<0.05) appeared in female heavy lambs. The percentage of fat trimmings in carcass and the tissue composition of sample cut were influenced by a significant interaction between age-class and sex (p<0.05): in males the age-class never affected the tissue composition of sample cut, as in females the muscle and fat percentages increased with age while the bone percentage decreased. The fat content of loin meat increased with age in females (p < 0.05) and decreased in males (p < 0.05). The poly-unsaturated fatty acids (FA) content of loin meat was higher in males than in females (p < 0.001), with saturated FA and mono-unsaturated FA revealing significant interactions between age-class and sex (p < 0.05). In conclusion, future implementation of genetic selection, oriented towards the improvement of meat production characteristics that are potentially present in the breed, is important